To develop a simple test for pancreatic exocrine function in patients with cystic fibrosis, we compared serum pancreatic amylase isoenzyme (P isoamylase) activity with the more complex standard tests of pancreatic function. Twenty-seven patients with cystic fibrosis, newborn to 46 years of age, were studied. All patients over 17 months old with evidence of pancreatic exocrine insufficiency, as manifested by abnormal duodenal secretions and/or abnormal 72-hour fecal fat absorption, had serum P isoamylase activity below the age-matched normal range; patients with adequate pancreatic function (aged 2 to 46 years) had P isoamylase activity in or above the normal range. Although both normal neonates and neonates with cystic fibrosis have very low levels of serum P isoamylase activity, in patients over 1 1/2 years of age serum P isoamylase activity may serve as a simple and useful discriminator of pancreatic exocrine function in patients with cystic fibrosis.